Project Summary: In the United States, rates of infectious disease-related hospitalizations and mortality have remained stable or increased significantly for those > 65 years of age, and the majority of these deaths are related to community-acquired pneumonia (CAP) and sepsis. Cytokines play a central role in the host defense mechanisms for patients with bacterial infectious diseases but may lead to septic shock or acute respiratory distress syndrome, and several common medications including statins, ACE inhibitors, and angiotensin receptor blockers (ARBs) have been demonstrated to reduce systemic inflammation due to cytokines. Several small studies have demonstrated that patients on statins or ACE inhibitors hospitalized with infectious disorders have improved clinical outcomes. However, further research is needed to clarify whether these medications may be beneficial in the care of patients with CAP and sepsis. The aims of this study are: 1) Determine the association between the outpatient use of medications of interest and clinical outcomes, including 30-day mortality, length of stay (LOS), and rates of mechanical ventilation for patients hospitalized with sepsis and CAP. 2) Determine the association between the inpatient continuation of medications of interest properties and clinical outcomes for patients hospitalized with CAP and sepsis. 3) To examine the impact of medication dosage of the most commonly used ACE inhibitor and statin upon 30-day mortality for patients hospitalized with CAP and sepsis. The proposed study is a retrospective, cohort study secondary data analysis of data gathered from several VA sources and merged to examine the impact of ACE inhibitors, ARBS, and statins upon important clinical outcomes for patients hospitalized with CAP and sepsis. The cohort will consist of all patients hospitalized in Department of Veterans Affairs (VA) hospitals with either CAP or sepsis in fiscal years 2002-2005 who received at least 1 year of primary care prior to admission. Data to obtained includes demographics, comorbid conditions, medications used as an outpatient and inpatient, and inpatient laboratory data, using the clinical databases of the VA health care system. Separate analyses will be performed for patients with sepsis and CAP. The primary outcome will be 30-day mortality, and secondary outcomes will be length of stay and rates of mechanical ventilation. The primary analyses will examine the impact of the medications of interest upon the clinical outcomes using generalized linear mixed-effect models. Relevance: Findings from this study will be used to determine a) whether randomized controlled trials testing the impact of these drugs on infectious disease outcomes should be conducted, and b) to better understand if these medications should be routinely recommended for populations at high-risk for pneumonia and/or sepsis. [unreadable] [unreadable] [unreadable] [unreadable]